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To improve our understanding of reproductive health and sexual function in women with cloacal malformations and other anorectal malformations (ARMs) METHODS: An observational cross-sectional survey was administered to individuals assigned female at birth aged 12 to 55 with ARMs and cloacal malformations cared for at our institution. Data included age of thelarche/menarche and questions on body image, gynecologic anatomy, sexual function, and pregnancy.Twenty-one patients responded in the ARM group and 30 in the cloacal malformation group. There were no differences in median age of thelarche/menarche in patients with ARMs (11/12.5 years) compared with patients with cloacal malformation (11/12 years). Patients with ARMs were more likely to have native vaginal tissue than those with cloacal malformations (n = 18, 82% vs n = 12, 40%; P = .03). There were no differences between groups regarding concerns about dyspareunia and functionality of their vagina (P.05). Forty-two percent of patients with cloacal malformations and 30% of patients with ARMs reported having been sexually active. Two patients with cloacal malformations and 2 with ARMs reported having been pregnant. Patients with cloacal malformations reported a lower quality of life score (80.4) compared with those with ARMs (87.0) (difference4.5).Patients with a cloacal malformation were less likely to have native vaginal tissue and reported a lower quality of life than those with ARMs. Despite this, patients with a cloacal malformation had similar reproductive health and sexual function compared with patients with ARMs. Our results reinforce the need for comprehensive sexual and reproductive health care for all women with ARMs.

To assess initial evaluation patterns of patients presenting to the Emergency Department (ED) with abnormal uterine bleeding (AUB) including differences by race DESIGN: Retrospective multicenter cohort study from October 2015 through September 2020 SETTING: Forty-seven children's hospitals submitting data to the Pediatric Health Information System PARTICIPANTS: Female patients aged 8-21 with an ED encounter with AUB as the primary diagnosis code INTERVENTIONS AND MAIN OUTCOME MEASURES: Proportion of visits with at least 1 laboratory assessment for the evaluation of anemia, iron deficiency, and/or hemostatic disorders RESULTS: We identified 17,759 unique patients with AUB seen in the ED who met inclusion criteria. Median age was 16.3 years (IQR, 14.1-17.8 years). Most encounters (n = 11,576, 65.2%) included evaluation for anemia, but only 6.8% (n = 1,215) included assessment for iron deficiency and 26.2% (n = 4,654) for hemostatic disorders. Black patients accounted for 34.7% (n = 6,155) of AUB encounters yet constituted only 25% of all ED encounters (n = 198,192). Black patients with AUB were less likely to undergo bleeding disorder evaluation (OR = 0.76; 95% CI, 0.69-0.83) but more likely to receive evaluation for sexually transmitted infections (OR = 1.63; 95% CI, 1.48-1.80) compared with White patients, despite controlling for age and concomitant pain.In a national cohort of adolescents presenting to the ED with AUB, evaluations for anemia and hemostatic disorders were infrequently performed, and racial differences existed regarding initial assessment. Further studies are needed to understand the factors underlying racial differences in hematologic testing and the impact of this disparity on health outcomes for females with AUB.

Context Pediatric patients receiving chemotherapy experience unwanted therapy-induced side effects, commonly constipation and pain that diminish quality of life. To date, few studies have investigated the safety and feasibility of osteopathic manipulative treatment (OMT) in pediatric oncology. Objectives The primary objective of this study is to investigate the safety and feasibility of OMT in pediatric oncology outpatient clinics. Methods This is a single institutional pilot study evaluating children aged ≥2–21 years receiving chemotherapy for an oncological diagnosis at Nationwide Children’s Hospital (NCH). Permission was obtained from the NCH Institutional Review Board. Participants were enrolled for 8 weeks and received weekly OMT. OMT was deemed feasible by participating in six out of eight weekly treatments, and safety was assessed through adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE). During the clinic visit, patients answered validated surveys on constipation (Bristol Stool Scale) and pain (FACES Scale) pre/post-OMT. Feasibility was analyzed utilizing a one-sided exact binomial test while validated tools and adverse events were summarized descriptively. Results A total of 23 patients were enrolled, with 21 included in feasibility analyses. The majority of the patients were female (n=13, 61.9%), with a median age of 12 years at enrollment (range, 2.7–20.8 years). There were no serious adverse events attributed to OMT intervention, and among the patients assessed for feasibility, 100% of them participated in at least two-thirds of their weekly OMT treatments, meeting our defined feasibility criteria. The intervention lasted an average of 14.2 min (range, 7.2–19.2 min). There were no FACES or Bristol Stool Scale scores that correlated with worsening pain on constipation post-OMT intervention. Conclusions Pediatric oncology patients were feasibly and safely able to receive OMT during a regularly scheduled chemotherapy visit. The limitations include the small sample size. These findings support the need to further investigate the safety and feasibility, as well as efficacy, of OMT in the pediatric oncology clinical setting.

To assess bleeding symptoms in patients with generalized joint hypermobility (GJH), compare bleeding scores to healthy historical pediatric controls, and determine if a correlation exists between Beighton scores and bleeding scores.Patients with GJH aged 6-21 years seen by rheumatology at Nationwide Children's Hospital in Columbus, Ohio were eligible. Participants/guardians completed the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool, a validated questionnaire defining presence, severity, and frequency of bleeding symptoms. Scores ≥ 3 have been associated with an underlying bleeding disorder in pediatric patients.Eighty-one patients agreed to participate. Median age was 13 years (IQR: 10-16 years) and mean Beighton score was 6.3 (range: 4-9). Commonly observed bleeding symptoms were oral bleeding (74%), easy bruising (59%), and bleeding with minor wounds (42%). Mean and median bleeding scores were 5.2 and 4, respectively, and were significantly higher than reported bleeding scores in pediatric controls, defined as those without bleeding symptoms or a previously diagnosed bleeding disorder (p0.001). Although 75% (95% CI: 64-84%) of patients had an abnormal bleeding score, only 12.3% were previously seen by hematology for bleeding symptoms. Among patients with GJH, higher Beighton scores were not associated with higher bleeding scores (Spearman's correlation -0.08).In a cohort of pediatric patients with GJH, three-quarters of participants had abnormal bleeding scores with mean bleeding score significantly elevated compared to healthy controls. We propose that screening for bleeding symptoms be integrated into routine care for GJH patients, with referral to hematology for patients with bleeding concerns. This article is protected by copyright. All rights reserved.

Sedation is often used to reduce pain and anxiety in pediatric patients with acute lymphoblastic leukemia (ALL) undergoing lumbar punctures (LPs). There is a potential for long-term effects on neurocognition with repeat sedative exposures in young children. The purpose of this study is to determine the practice habits regarding sedation for LPs in pediatric patients with ALL among multiple institutions.This is a retrospective study of 48 hospitals in the Pediatric Health Information Systems (PHIS) between October 2015 and December 2019. Children 1 to 18 years old with ALL who received intrathecal chemotherapy in an outpatient setting were included. We analyzed the prevalence of anesthesia usage and the types of anesthetics used.Of the 16,785 encounters with documented use of anesthetic medications, intravenous and inhaled anesthetics were used in 16,486 (98.2%) and local anesthetics alone in 299 (1.8%). The most commonly used medications used for sedation were propofol (n=13,279; 79.1%), midazolam (n=4228; 25.2%), inhaled fluranes (n=3169; 18.9%), and ketamine (n=2100; 12.5%).The majority of children's hospitals in the United States use intravenous and inhaled anesthetics for routine therapeutic LPs in pediatric patients with ALL. Propofol is one of the most common medications used for sedation.

There is paucity of data on COVID-19 vaccine hesitancy amongst parents of pediatric (age ≤ 17 years) hematopoietic cell transplant (HCT) recipients. We conducted a cross-sectional study to determined COVID-19 vaccine hesitancy, and COVID-19 impact on family and related distress in this population. A national group (n = 80) was recruited via social media (Facebook) from February−May 2021. With vaccine approval for ≥12 years in July 2021, a second group (n = 37) was recruited locally. Parents completed surveys including the Vaccine Hesitancy Questionnaire and COVID-19 Exposure and Family Impact Scale (CEFIS). Nonparametric statistics were used to analyze results and factors impacting Vaccine Hesitancy Scores (VHS). The majority of parents were non-Hispanic White (≥90%) and children ≥3 months post-HCT (85%). Mean CEFIS score (scale 0–60) was 41.11 (SD = 8.24), with higher scores indicating negative impact of the pandemic. Mean (± standard deviation) VHS was 2.87 (±0.79) on a scale of 1–4, with 1 indicating higher and 4 lower hesitancy. Concerns about vaccine related side effects, lower parental age, child age, household income, and education were associated with lower VHS. Receiving reliable information and recommendations by providers was associated with higher VHS. Improving vaccine acceptance in this population is critical in protecting pediatric HCT recipients.

In August 2022, the Florida Department of Health (FDOH) was notified of a suspected case of monkeypox in an infant aged2 months who was admitted to a Florida hospital with a rash and cellulitis. This case report highlights findings from the related epidemiologic investigation and describes the public health actions taken. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* This is the youngest patient with confirmed monkeypox infection in Florida to date.

T cells redirected to cancer cells either via a chimeric antigen receptor (CAR-T) or a bispecific molecule have been breakthrough technologies; however, CAR-T cells require individualized manufacturing and bispecifics generally require continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics via adeno-associated virus (AAV) gene transfer. We demonstrate proof of principle in a CD19 + lymphoma xenograft model using a single intravenous dose of AAV expressing a secreted version of blinatumomab, which could serve as a universal alternative for CD19 CAR-T cell therapy. In addition, we created an inducible version using an exon skipping strategy and achieved repeated, on-demand expression up to at least 36 weeks after AAV injection. Our system could be considered for short-term and/or repeated expression of other transgenes of interest for noncancer applications.

Introduction In the era of electronic medical records, pen-and-paper-based physician-administered bleeding assessment tools (BAT) remain under-utilized in the clinical setting, as they are noted to be time-consuming. Aim The current study reviews the use of an electronic self-administered bleeding assessment tool (eBAT) prospectively in a paediatric haematology clinic and in comparison with a physician administered BAT (pBAT). Materials and methods This was reviewed and approved in the current form because the aims statement includes the method regarding comparison of 2 groups. So no additional section required. Results A total of 94 BAT response pairs were available for analysis. The median time required for patients or parents to complete the eBAT was 8 min, with less than a third of the patients requiring over 10 min. The median bleeding scores noted in this study were 4 for both the BATs, with strong positive correlation between the eBAT and the physician administered bleeding questionnaire. The eBAT had a sensitivity of 93.8% (95% CI 82.8%-98.7%), a specificity of 34.8% (95% CI 21.4%-50.3%), a positive predictive value (PV) of 60.0% (95% CI 54.5%-65.2%) and a negative PV of 84.2% (95% CI 62.5%-94.5%) for identifying a bleeding disorder. Conclusions Findings indicate that eBAT is a valid and time-efficient screening tool for evaluating patients' bleeding symptoms, which can improve clinical applicability of BATs by reducing time for bleeding history review.

Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru.Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997-2008 and 2009-2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test).Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The 5-year OS was 62% (95% CI: 53%-74%), while EFS was 57% (95% CI: 48%-69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31-60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009-2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03).Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009-2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

BACKGROUND Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (

Perovskite oxides continue to attract huge interest due to their fascinating and wide-ranging properties for diverse applications. The tunability of these properties may be further enhanced by incr...

The Accreditation Council for Graduate Medical Education requires Milestone-based assessments of residents and fellows. In pediatrics, 11 subcompetencies are common to both residency and subspecialty fellowship training. It is unknown whether Milestone scores achieved during residency are related to Milestone scores achieved in early fellowship.To assess the relationship between final residency Milestones scores and first-year fellowship Milestones scores in the 11 common subcompetencies (CSCs) across pediatric subspecialties.This was a retrospective single-institution cohort study of pediatric fellows beginning fellowship training between July 2016 and July 2019. De-identified Milestone score sets for final residency scores (R), mid-year first-year fellowship scores (F1), and final first-year fellowship scores (F2) were collected. Spearman correlation and regression analyses were used to assess score relationships.Data for 85 of 98 eligible fellows were collected. Consistently, the F1 scores were lowest, and the R scores were highest. There was a weak positive correlation between the composite R scores and the composite F1 scores. There was a weak positive correlation between residency and fellowship scores for 6 CSCs and no significant correlation for the remaining 5.For the 11 pediatric CSCs, the final residency Milestone scores are consistently higher than and only weakly associated with early fellowship Milestone scores. There may be limitations to the use of residency scores for fellowship program directors in guiding individualized education for early fellows. This study provides groundwork for additional study of Milestone relationships and may help inform the next iteration of pediatric subspecialty Milestones.

To evaluate the use of intrauterine devices (IUDs) in two young women's hematology clinics and compare adverse events in adolescents with and without inherited bleeding disorders (BDs) DESIGN: Retrospective multicenter cohort study from February 2014 through February 2020 SETTING: Young women's hematology clinics at Nationwide Children's Hospital in Columbus, Ohio, and Children's Medical Center in Dallas, Texas PARTICIPANTS: Female patients evaluated for heavy menstrual bleeding (HMB) who underwent IUD placement INTERVENTIONS AND MAIN OUTCOME MEASURES: Rates of IUD expulsion, malposition, and ongoing HMB requiring additional medical treatment RESULTS: We identified 43 patients with BDs and 35 patients without BDs who underwent placement of an IUD for HMB. The mean age was 14.9 years (range 11.0-21.4 years) at the time of presentation and 15.8 years (range 11.0-21.4 years) at IUD placement. Those with BDs were younger at the time of IUD insertion. Most patients (90%) had previously failed other methods to control HMB. The annual rate of IUD adverse events was 0.25 per year of use, and all adverse events occurred in the first 20 months after placement. There were no significant differences in adverse IUD events in patients with and without BDs, although those without BDs requested IUD removal more frequently.In this cohort of adolescent females, the presence of a BD was not associated with a higher IUD expulsion rate. IUD placement should be considered a first-line option for adolescents with BDs who experience HMB.

Childhood acute lymphoblastic leukemia (ALL) fortunately has high survival rates, and understanding longer term implications of therapy is critical. In this study, we aimed to investigate kidney health outcomes by assessing the prevalence of renal dysfunction and hypertension (HTN) in children with ALL at 1-5 years after ALL diagnosis.This was a single-center, cross-sectional study of children with ALL who were 1-5 years post diagnosis. Glomerular filtration rate (GFR) measurements were calculated, and urine samples were collected to assess for protein/creatinine and albumin/creatinine. Blood pressure (BP) was determined by standard oscillometric technique, and children ≥6 years of age were eligible for ambulatory blood pressure monitoring (ABPM).Forty-five patients enrolled in the study, and 21 completed ABPMs. Fifteen patients (33%, 95% CI: 20%-49%) developed acute kidney injury (AKI) at least once. Thirteen (29%, 95% CI: 16%-44%) had hyperfiltration, and 11 (24%) had abnormal proteinuria and/or albuminuria. Prevalence of HTN based on clinic measurements was 42%. In the 21 ABPM patients, 14 had abnormal results (67%, 95% CI: 43%-85%), with the majority (11/21) demonstrating abnormal nocturnal dipping pattern.Among children with ALL, there is a high prevalence of past AKI. The presence of hyperfiltration, proteinuria, and/or albuminuria at 1-5 years after ALL diagnosis suggests real risk of developing chronic kidney disease (CKD) over time. There is a high prevalence of HTN on casual BP readings and even higher prevalence of abnormal ABPM in this group. The high prevalence of impaired nocturnal dipping by ABPM indicates an increased risk for future cardiovascular or cerebral ischemic events.

Under radiative environments such as extended hard X- or γ-rays, degradation of scintillation performance is often due to irradiation-induced defects. To overcome the effect of deleterious defects, novel design mitigation strategies are needed to identify and design more resilient materials. The potential for band-edge engineering to eliminate the effect of radiation-induced defect states in rare-earth-doped perovskite scintillators is explored, taking Ce3+-doped LuAlO3 as a model material system, using density functional theory (DFT)-based DFT + U and hybrid Heyd-Scuseria-Ernzerhof (HSE) calculations. From spin-polarized hybrid HSE calculations, the Ce3+ activator ground-state 4f position is determined to be 2.81 eV above the valence band maximum in LuAlO3. Except for the oxygen vacancies which have a deep level inside the band gap, all other radiation-induced defects in LuAlO3 have shallow defect states or are outside the band gap, that is, relatively far away from either the 5d1 or the 4f Ce3+ levels. Finally, we examine the role of Ga doping at the Al site and found that LuGaO3 has a band gap that is more than 2 eV smaller than that of LuAlO3. Specifically, the lowered conduction band edge envelopes the defect gap states, eliminating their potential impact on scintillation performance and providing direct theoretical evidence for how band-edge engineering could be applied to rare-earth-doped perovskite scintillators.

Background: Existing research shows that hypoglycemia fear (HF) is common in parents of children with established type 1 diabetes (T1D). We examined parental HF in the T1D recent-onset period and evaluated whether continuous glucose monitoring (CGM) adoption relates to improved outcomes of parental HF. Methods: In TACKLE-T1D, a prospective study of five- to nine-year olds with recent-onset T1D, parents completed the Hypoglycemia Fear Survey-Parents (HFS-P) at baseline (T1) and 6 (T2) and 12 (T3) months post-baseline. The HFS-P measures worry about hypoglycemia (HFS-Worry score) as well as hypoglycemia avoidance behaviors (HFS-Behavior score). We recorded CGM start dates for youth during the same time period through medical record review. Results: Between T1 and T2, 31 youth (32.3%) initiated CGM therapy, and between T2 and T3, an additional 17 youth (17.7%) began using CGM, leaving 48 youth who never initiated CGM therapy (50%) in the recent-onset period. Parents reported moderate HFS-Worry scores at T1 (32.9 ± 11.9), which increased between T1 and T2 (37.6 ± 11.4, P < .001) and plateaued between T2 and T3 (37.7 ± 12.4, P = .89). In contrast, parental HFS-Behavior scores decreased between T1 (33.1 ± 5.8) and T2 (32.2 ± 6.0, P = .005) and plateaued between T2 and T3 (32.2 ± 6.0, P = .95). Baseline HFS-Behavior and Worry scores were associated with increased adoption of CGM between T1-T2 and T2-T3, respectively. Parents of children initiating CGM therapy between T1 and T2 showed the largest decrease in HFS-Behavior ( P = .03). Conclusions: Initiating CGM therapy within the first 12 months of T1D may help reduce parents’ use of hypoglycemia avoidance behaviors, but has little effect on parents’ hypoglycemia worry.

Heteroanionic oxysulfide perovskite compounds represent an emerging class of new materials allowing for a wide range of tunability in the electronic structure that could lead to a diverse spectrum of novel and improved functionalities. Unlike cation ordered double perovskites—where the origins and design rules of various experimentally observed cation orderings are well known and understood—anion ordering in heteroanionic perovskites remains a largely uncharted territory. In this contribution, we present and discuss insights that have emerged from our first-principles-based electronic structure analysis of a prototypical anion-ordered SrHf(O0.5S0.5)3 oxysulfide chemistry, studied in all possible anion configurations allowed within a finite size supercell. We demonstrate that the preferred anion ordering is always an all-cis arrangement of anions around an HfO3S3 octahedron. As a general finding beyond the specific chemistry, the origins of this ordering tendency are traced back to a combined stabilization effect stemming from electronic, elastic, and electrostatic contributions. These qualitative notions are also quantified using state-of-the-art machine learning models. We further study the relative stability of the identified ordering as a function of A (Ca, Sr, Ba) and B (Ti, Zr, Hf) site chemistries and probe chemistry-dependent trends in the electronic structure and functionality of the material. Most remarkably, we find that the identified ground-state anion ordering breaks the inversion symmetry to create a family of oxysulfide ferroelectrics with a macroscopic polarization >30 μC/cm2, exhibiting a significant promise for electronic materials applications.

OBJECTIVE To monitor occurrence of stressful life events, assess correlations with family functioning and parental psychosocial measures, and examine the impact of stressful life events on diabetes management in the first year after diagnosis of type 1 diabetes (T1D) in children using a mixed methods design. METHODS In a prospective study of 5- to 9-year-olds with recent-onset T1D (mean age 7.4 ± 1.3 years, T1D duration 4.7 ± 3.3 months), we monitored glycated hemoglobin A1c (HbA1c), income, job status, family health, and marital status at baseline and every 3 months up to 1 year. We measured coping, parental depression, and diabetes family conflict at baseline. RESULTS Of 128 families, 53.9% (n = 69) reported 1+ stressful event, with 25.8% reporting income change (n = 33) during this period, 23.4% additional family health changes (n = 30), 22.7% job changes (n = 29), 21.9% changes in child's school (n = 28), and 3.9% changes in marital status (n = 5). Baseline active avoidance coping, parental depression, and diabetes family conflict correlated with a higher number of stressful life events (r = 0.239, P

This article provides an ecological model of child support facilitation through broad efforts to maintain high rates of paternity establishment via agency–university collaboration. The study utilized administrative data (2,208 electronic records from the Bureau of Health Statistics) on voluntary paternity affidavits (VPA) rejected by the Iowa Department of Public Health. These records represented all rejected VPAs from 70 hospitals in Iowa for 6 months in 2017. Results indicated that the majority of VPAs were not accepted for minor errors (78%) such as missing information rather than incorrect information. Results also indicated variation among hospitals and hospital regions in the reasons for rejection. Outreach to hospitals targeting affidavit completion is a potential step for increasing paternity establishment.

Malnutrition during cancer treatment increases treatment-related morbidity and mortality. Our study better characterizes variability in malnutrition identification and treatment by examining nutrition-related diagnoses and support for children with central nervous system (CNS) and non-CNS solid tumors during therapy. We examined diagnosis of malnutrition, use of tube feeding or parenteral nutrition (PN), and appetite stimulants.We retrospectively reviewed 0 to 21-year-old patients in the Pediatric Health Information System from 2015 to 2019. Patients were classified as having (1) billed malnutrition diagnosis, (2) malnutrition diagnosis or using PN and enteral nutrition ("functional malnutrition"), and (3) any previous criteria or prescribed appetite stimulants ("possible malnutrition"), as well as associated risk factors.Among 13,375 unique patients, CNS tumors were most common (24.4%). Overall, 26.5% of patients had malnutrition diagnoses, 45.4% met functional malnutrition criteria, and 56.0% had possible malnutrition. Patients with adrenal tumors had highest billed, functional, and possible malnutrition (36.6%, 64.1%, and 69.4%, respectively) followed by CNS tumors (29.1%, 52.4%, and 64.1%). Patients with adrenal tumors had highest rates of PN use (47.4%) and those with CNS tumors had the highest tube feeding use (26.8%). Hospital admissions with malnutrition had a longer hospital length of stay (LOS) (6 vs 3 days, P 0.0001), more emergency department admissions (24.4% vs 21.8%, P 0.0001), and more opioid use (58.6% vs 41.4%, P 0.0001).Variability in malnutrition diagnoses hinders clinical care and nutrition research in pediatric oncology. Improving disease-specific recognition and treatment of malnutrition can target nutrition support, ensure appropriate reimbursement, and potentially improve outcomes for children with solid tumors.

OBJECTIVES In 2009, a large multicenter study demonstrated that the rate of pediatric venous thromboembolism (VTE) across US children’s hospitals had significantly increased from 2001 to 2007. The objective of this study was to evaluate the rate of pediatric VTE from 2008 to 2019 using similar methodology. METHODS A retrospective cohort study using the Pediatric Health Information System (PHIS) database. Subjects from birth to RESULTS During the 12-year study period, there were 52 401 hospital admissions among 39 713 pediatric patients with a diagnosis of VTE. The VTE admission rate increased from 46 VTE cases per 10 000 admissions in 2008 to 106 VTE cases per 10 000 admissions in 2019, a 130% increase (P < .0001) in VTE events. The median age at admission was 6.1 years, and almost one-third (31.3%) of patients with VTE were in the adolescent age group (13–17 years). Most patients (78%) had an underlying chronic medical condition. CONCLUSIONS The rate of VTE in hospitalized pediatric patients continues to increase from a 70% increase reported from 2001 to 2007 to the 130% increase from 2008 to 2019. These findings support the need for more effective VTE prevention strategies. Clinical trials focused on risk stratification and VTE prevention are needed.

BACKGROUND: A standard-of-care has not been established for the management of patients with Down syndrome (DS) who develop primary central nervous system (CNS) germ cell tumors (GCTs) – the most common CNS neoplasm in DS – despite being more susceptible to treatment-related adverse events. METHODS: Data from large academic institutions were collected and a comprehensive review of the medical literature was conducted. RESULTS: Ten patients from six institutions (five USA, one Brazil) were reviewed. Additionally, thirty-one patients were identified in the literature from 1975-2021. Of the 41 total patients, mean age was ten years (range, birth to 35 years); males were predominant (61%). Basal ganglia were the most common tumor location (n=12; 29%), followed by posterior fossa (n=7; 17%). Sixteen patients had non-germinomatous germ cell tumors (NGGCTs) (39%), 14 had pure germinomas (34%), and eight had teratomas (20%); histology was unreported for two (5%). Nine patients (22%) experienced disease relapse, of which four died from tumor progression (one germinoma versus three teratoma). Fifteen patients (37%) experienced treatment-related complications - seven died (four germinoma versus three NGGCT). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, and one from Moyamoya following radiation-therapy (RT) only. Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival (OS) was 66% for all histological types - 62% germinoma, 79% for NGGCT, and 53% for teratoma. Three-year OS for patients who received RT or chemotherapy was 71% and 75% respectively. Twenty-seven patients remain alive at latest follow-up (mean follow-up from diagnosis: 46.8 months). CONCLUSIONS: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered for this patient population to mitigate treatment-related complications and long-term neurocognitive sequelae.

To define the incidence of acute kidney injury (AKI), chronic kidney disease (CKD), and hypertension (HTN) in pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) over a recent 9-year period.This study is a retrospective cohort study of all pediatric patients diagnosed with ALL at Nationwide Children's Hospital from January 1, 2008, to December 31, 2016. Patient demographic and clinical data including serum creatinine and blood pressure were collected at diagnosis up to 9 years post diagnosis.A total of 222 patients were identified for this study. The overall incidence of AKI in our cohort was high, with 101 subjects (45.5%, CI 38.8-52.3%) developing AKI at least once. CKD status could only be determined in 214 patients due to limited later GFR data. The incidence of CKD was low with only 5 of 214 patients developing CKD (2.3%, CI: 0.8-5.4%). The overall incidence of HTN at diagnosis was 45.6% (95% CI: 59.1-72%), and at 1 month post diagnosis was 65.8% (95% CI: 59.1-72.0%). Chronic HTN could only be determined in 216 patients due to limited blood pressure data. Chronic HTN was noted in 34.3% of patients (74/216, 95% CI: 28-41%).Among children with ALL, the incidence of AKI is relatively high at the time of diagnosis. However, development of CKD is relatively rare, suggesting good mid-term kidney prognosis. There is a high incidence of HTN at the time of diagnosis, 1 month post diagnosis, and chronic HTN that often goes untreated. A higher resolution version of the Graphical abstract is available as Supplementary information.

Diffusion of Xe atoms in UO2 fuel is important for nuclear fuel performance, and is enabled by interaction with U and O vacancies. Previous work using atomistic calculations based on density functional theory (DFT) and empirical potentials (EP) focused on the role of small vacancy clusters ( Xe U 2 O y , y = 0, 1, 2) for Xe transport, but the model predictions failed to reproduce the experimental observations by consistently underestimating Xe diffusivity. In this work, where we focused on out-of-pile conditions (i.e. in the absence of irradiation), we have explored two of the uncertainties associated with the model: the DFT methodology and the types of clusters considered. We found that using the energy barriers obtained with GGA + U DFT allows to reconcile simulation results and experimental observations in the intrinsic regime (i.e. out-of-pile conditions). The XeUO cluster is the preferred configuration at high temperature, while the mobile Xe U 2 O cluster takes over below 1720 K. The latter cluster is also the main contributor to Xe diffusion and good agreement is obtained with current models empirically fitted to experiments for diffusion at high temperature. A simple expression that captures most of Xe diffusivity is proposed, relying on XeUO and Xe U 2 O clusters only. We also determined the out-of-pile concentration and diffusivity of extended clusters Xe U x O y , 3 ≤ x ≤ 9 , and determined that these do not contribute significantly to the overall diffusivity under intrinsic conditions. However, we speculate that the Xe U 4 O 3 and Xe U 8 O 9 clusters, which have relatively low migration barrier, may play a role under irradiation conditions, because the radiation-induced enhanced vacancy concentration would rapidly increase the fraction of large Xe-vacancy clusters.

Hematopoietic cell transplantation (HCT) is the sole curative option for congenital dyserythropoietic anemia (CDA), a rare type of hemolytic anemia characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. In this retrospective multicenter study, we report the outcomes of children with CDA who underwent HCT at participating Pediatric Transplantation and Cellular Therapy Consortium centers. Clinical information on HCT and associated outcomes was collected retrospectively using a common questionnaire. Data were analyzed using descriptive statistics and appropriate analysis. Eighteen patients with CDA who underwent allogeneic HCT between 2002 and 2020 were identified. The majority of patients (n = 13) had CDA type II, and the remainder had either CDA type I (n = 2) or CDA of unknown type (n = 3). Mutations were identified in 7 patients (39%), including SEC23B in 5, GATA1 in 1, and abnormality of chromosome 20 in 1. Thirteen patients had evidence of iron overload pre-HCT and received chelation therapy for a median duration of 10 months (range, 2 months to 17 years) pre-HCT. The median age at the time of HCT was 5.5 years (range, 0.7 to 26 years). Donors were HLA-matched (sibling, 4; unrelated, 10) and mismatched (haploidentical, 1; unrelated, 3). Graft sources were bone marrow in 15 patients, umbilical cord blood in 2 patients, or both in 1 patient. Conditioning included busulfan-based myeloablative (67%), fludarabine-based reduced-intensity (27%), or nonmyeloablative (6%) regimens. Five patients developed veno-occlusive disease, and 4 had viral reactivation. The cumulative incidence of acute graft-versus-host disease (GVHD) was 33%, and that of chronic GVHD was 22%. Four patients (22%) experienced graft failure; all engrafted following either a second HCT (n = 2) or third HCT (n = 2) but sustained considerable morbidities (3 GVHD, 1 death, 2 viral reactivation). With a median follow-up of 3.2 years (range, 0.6 to 14 years)), the 2-year overall survival, event-free survival (EFS), and GVHD-free EFS were 88% (95% confidence interval [CI], 73% to 100%), 65% (95% CI, 45% to 92%), and 60% (95% CI, 40% to 88%), respectively. Univariate analysis did not identify any patient- or transplantation-related variables impacting outcomes. Our study indicates that HCT can be curative for patients with CDA. Strategies such as aggressive chelation, use of preconditioning therapy, and early HCT in the presence of a suitable donor before comorbidities occur are needed to improve engraftment without increasing the risk for toxicity and mortality.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with Medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997-2013, data from 103 children older than three years with Medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997 – 2008 and 2009 – 2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, while prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The five-year OS was 62% (95% CI: 53 – 74%) while EFS was 57% (95% CI: 48 – 69%). The variables adversely affecting survival were anaplastic histology [compared to desmoplastic; OS: HR=3.4, p=0.03], metastasis [OS: HR=3.5, p=0.01; EFS: HR=4.3, p=0.004], delay in radiation therapy of 31-60 days [compared to ≤30 days; EFS: HR=2.1, p=0.04], and treatment 2009 – 2013 cohort[OS: HR=2.2, p=0.02; EFS: HR=2.0; p=0.03]. CONCLUSIONS: Outcomes for Medulloblastoma at INEN were low compared with HIC. Anaplastic sub-type, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009 - 2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

Despite recommendations for vaccination after hematopoietic cell transplantation (HCT), immunization rates remain low leaving children at high risk for vaccine preventable infections (VPIs). However, the burden from VPIs in pediatric HCT recipients is not well known. We describe the prevalence, risk factors, and outcomes of VPI-associated hospitalizations at centers participating in the Pediatric Health Information System database. Children18 years who underwent allogeneic or autologous-HCT between 1/1/2010-31/12/2018, were identified and prevalence of overall VPI and of each infection were determined at five time-points within 5 years post-HCT. In total, 684 of 9591 pediatric HCT recipients had a VPI-associated hospitalization, most frequently in the first 6-12 months, for an overall prevalence of 7.1% (95% CI: 6.6-7.7%). Influenza, varicella, and invasive pneumococcal infections were the most frequent. Multivariable analyses identified younger age (OR = 0.96 [95% CI: 0.93-0.99]; p = 0.013), primary immune deficiency (PID) (OR = 1.78 [95% CI: 1.11-2.84]; p = 0.016), and GVHD (OR = 1.62 [95% CI: 1.05-2.48]; p = 0.028) as independent risk factors during the initial HCT-hospitalization. Children with VPI had longer duration of hospitalization (55[51] vs 36[24] days, p 0.001)

Mesenchymal stromal cells (MSCs) possess remarkable tumor tropism, making them ideal vehicles to deliver tumor-targeted therapeutic agents; however, their value in clinical medicine has yet to be realized. A barrier to clinical utilization is that only a small fraction of infused MSCs ultimately localize to the tumor. In an effort to overcome this obstacle, we sought to enhance MSC trafficking by focusing on the factors that govern MSC arrival within the tumor microenvironment. Our findings show that MSC chemoattraction is only present in select tumors, including osteosarcoma, and that the chemotactic potency among similar tumors varies substantially. Using an osteosarcoma xenograft model, we show that human MSCs traffic to the tumor within several hours of infusion. After arrival, MSCs are observed to localize in clusters near blood vessels and MSC-associated bioluminescence signal intensity is increased, suggesting that the seeded cells expand after engraftment. However, our studies reveal that a significant portion of MSCs are eliminated en route by splenic macrophage phagocytosis, effectively limiting the number of cells available for tumor engraftment. To increase MSC survival, we transiently depleted macrophages with liposomal clodronate, which resulted in increased tumor localization without substantial reduction in tumor-associated macrophages. Our data suggest that transient macrophage depletion will significantly increase the number of MSCs in the spleen and thus improve MSC localization within a tumor, theoretically increasing the effective dose of an anti-cancer agent. This strategy may subsequently improve the clinical efficacy of MSCs as vehicles for the tumor-directed delivery of therapeutic agents.

The sacral ratio has been used as a tool for evaluating sacral development in patients with anorectal malformations. Sacral ratios can be calculated by obtaining sacral radiographs in the anteroposterior (AP) and lateral planes.The objective of the study was to determine the correlation and agreement in sacral ratio calculations.In this single institution retrospective cohort study, we reviewed medical charts of all pediatric anorectal malformation patients treated between March 2014 and September 2018 who had both AP and lateral images of their sacrum. All sacral ratios were measured by three radiologists. Pearson's correlation coefficients and corresponding 95% confidence intervals (CIs) were used to assess the correlation between the AP and lateral radiographs. A weighted Kappa statistic was used to measure the agreement between how the AP and lateral sacral ratios categorized observations into risk groups.Our initial cohort consisted of 646 observations from patients with anorectal malformations who had radiographs obtained in both AP and lateral planes. We excluded all observations (n=76) where the radiographs were deemed to be inadequate or not appropriately centered to measure sacral ratio. For a given pair of measurements, the mean lateral sacral ratio was 0.07 units greater than the AP plane (95% CI 0.06-0.09, paired t-test P-value0.0001). AP and lateral images had a moderate positive correlation (Pearson's r=0.76, 95% CI 0.73-0.79, P0.0001) and moderate agreement in risk categorization (unweighted kappa = 0.60, P0.0001). AP and lateral readings conducted by all three radiologists had excellent inter-rater reliability with intraclass correlations for AP and lateral sacral ratios of 0.88 and 0.84, respectively.Even though the AP and lateral sacral ratios had moderate positive correlation, the mean sacral ratio determined by images in the lateral plane was 0.07 units greater than the AP plane. AP and lateral sacral ratios concluded different risk categories relatively often. Future studies are needed to determine whether AP or lateral sacral ratios correlate better with continence in patients with anorectal malformations.

The most commonly reported gastrointestinal (GI) manifestations of COVID-19 include abdominal pain, diarrhea, nausea and vomiting. There is limited data regarding GI bleeding in patients with COVID-19, however, patients have been documented to present with hematochezia or melena at the onset of COVID-19 symptoms. The presence of GI bleeding in the setting of COVID-19 complicates the patient's clinical course and management of sequelae including coagulopathy. Clinicians should be aware of a possible increased risk of GI bleeding and its complications when managing critically ill COVID-19 patients.

OBJECTIVE To describe sociodemographic and clinical characteristics of youth and young adults with type 1 diabetes who endorsed suicidal ideations as part of routine depression screening and the results of their suicide risk assessments. RESEARCH DESIGN AND METHODS The Patient Health Questionnaire–9 was used to assess depressive symptoms and suicide/death ideation in 550 youth and young adults with type 1 diabetes ages 10–24 years. Only individuals who endorsed suicidal/death ideations (n = 49) completed a standardized suicide risk assessment protocol and safety planning. RESULTS Nine percent of individuals endorsed suicidal/death ideation and of those, 83.4% reported clinically elevated depressive symptoms; 16% made a previous suicide attempt. No youth (n = 39) or young adults (n = 11) disclosed current plans or preparations for suicide, but five who expressed suicidal ideation acknowledged the lethality of insulin for an attempt. Three previously used insulin to attempt suicide. The overwhelming majority of individuals were classified as being low risk for future suicide attempt/completion. None were hospitalized as a part of the suicide risk assessment, and no suicide completions have occurred. CONCLUSIONS The findings of this study provide initial insight into the behaviors and cognitions of youth and young adults with type 1 diabetes who experience suicidal and death ideations. Comprehensive suicide risk assessment and safety planning are feasible during routine type 1 diabetes clinic appointments.

The defect relaxation volumes obtained from density-functional theory (DFT) calculations of charged vacancies and interstitials are much larger than their neutral counterparts, seemingly unphysically large. We focus on UO2 as our primary material of interest, but also consider Si and GaAs to reveal the generality of our results. In this work, we investigate the possible reasons for this and revisit the methods that address the calculation of charged defects in periodic DFT. We probe the dependence of the proposed energy corrections to charged defect formation energies on relaxation volumes and find that corrections such as potential alignment remain ambiguous with regards to its contribution to the charged defect relaxation volume. We also investigate the volume for the net neutral defect reactions comprising individual charged defects, and find that the aggregate formation volumes have reasonable magnitudes. This work highlights the issue that, as is well-known for defect formation energies, the defect formation volumes depend on the choice of reservoir. We show that considering the change in volume of the electron reservoir in the formation reaction of the charged defects, analogous to how volumes of atoms are accounted for in defect formation volumes, can renormalize the formation volumes of charged defects such that they are comparable to neutral defects. This approach enables the description of the elastic properties of isolated charged defects within an overall neutral material.

Additives are widely used to control the microstructure of materials via their effect on defect chemistry during sintering. As the primary nuclear fuel, the properties of UO2 are crucial for safe and efficient reactor operation. UO2 has been manipulated by fuel vendors through doping to enhance grain size to provide improved fission gas retention and plasticity. In this work the common phenomenon that governs the effect of Mg, Ti, V, Cr, Mn, and Fe doping of UO2 for enhanced grain growth is revealed, elucidating experimental observations. A combined density functional theory and empirical potential description of defect free energy is used to calculate the doped UO2 defect concentrations as a function of temperature. At high (sintering) temperatures all dopants studied transition to a positively charged interstitial defect. Furthermore, a number of dopants (Ti, V, Cr, and Mn) do so in sufficiently high concentrations to greatly increase the negatively charged uranium vacancy concentration. High uranium vacancy concentrations can enhance grain growth and fission gas diffusion. Mg and Fe also enhance uranium vacancy concentrations but to a lesser extent, while Al has no impact. The enhanced uranium vacancy concentrations, associated with solution of dopants interstitially, is proposed as the mechanism responsible for the enlarged grains seen experimentally in (Ti/V/Cr/Mg)-doped systems. Mn- and V-doped UO2 have been predicted to have higher uranium vacancy concentrations than the more widely used Cr-doped UO2, leading to higher grain growth and fission gas diffusivity.